AB0818 SCLERODERMA RENAL CRISIS TREATMENT WITH C5 INHIBITOR ECULIZUMAB – A REVIEW OF LITERATURE
Authors: L. Farrukh, H. H. Waqar, S. Mehta, L. Shapiro
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Scleroderma renal crisis (SRC) occurs in about 10% of SSc patients and is characterized by abrupt onset of hypertension, thrombotic microangiopathy (TMA), and acute kidney injury. Although prognosis has improved with the use of angiotensin-converting enzyme inhibitors (ACE-i), 40% of SRC patients still require dialysis, and 20-25% die within 1 year. The pathogenesis of SRC remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease [1]. It is hypothesized that injury to the endothelium due to persistent stimulation by the complement system creates a pathological loop responsible for thrombotic microangiopathy and target organ injury. Several case reports have shown that Eculizumab (humanized recombinant immunoglobulin G2/4 monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who presented with symptoms of thrombotic microangiopathy [2,3]. <h3>Objectives</h3> In this study, we aimed to characterize the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab. <h3>Methods</h3> A literature search was conducted on PubMed and Cochrane from inception to December 2022 using MeSH terms for 'scleroderma', 'systemic sclerosis' 'scleroderma renal crisis', 'Eculizumab', and 'Solaris'. We included case reports, case series, observational studies, and literature reviews. We included patients with treatment refractory SRC who did not show improvement with ACE inhibitors or patients who had evidence of thrombotic microangiopathy (SRC-TMA). <h3>Results</h3> The initial search revealed 27 articles. After exclusion of non-relevant articles, data was included from 11 articles and 16 patients. The median age was 51 years, sex distribution was 4 males (33.3%) and 12 females (66.6%). Treatment with ACE-i was reported in 11 (68.75%), plasmapheresis (PLEX) in 8 (50%), steroids in 5 (31.25%), cyclophosphamide (CYC) in 3 (18.75%), calcium channel blockers (CCB) in 2 (12.5%) and Rituximab (RTX) in 2 (12.5%) of the patients. Renal replacement therapy (RRT) was required in 10 patients (62.5%). 8 out of 10 patients (80%) were reported to have clinical improvement with Eculizumab (Eculi) therapy <b>(Table 1).</b> <h3>Conclusion</h3> Recent clinical studies have focused on the role of complement activation in the pathogenesis of SRC and results suggest the use of C5 inhibitor in the treatment of refractory SRC. Serum complement levels and renal histological findings could help us identify patients who could benefit from Eculizumab. These findings should prompt testing on a larger cohort of SRC-TMA patients. However, based on the positive anecdotal evidence, it is reasonable to treat SRC patients with eculizumab in whom complement-mediated TMA is suspected. <h3>References</h3> [1]Cole, Alice, Voon H. Ong, and Christopher P. Denton. "Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis." <i>Clinical Reviews in Allergy &amp; Immunology</i> (2022): 1-14. [2]Devresse, Arnaud, et al. "Complement activation and effect of eculizumab in scleroderma renal crisis." <i>Medicine</i> 95.30 (2016). [3]Uriarte, Maite Hurtado, Carolina Larrarte, and Laura Bravo Rey. "Scleroderma renal crisis debute with thrombotic microangiopathy: a successful case treated with eculizumab." <i>Case Reports in Nephrology</i> 2018 (2018). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.